The neural circuitry of the dorsal horn of the spinal cord forms the basis for the mechanisms of pain and analgesia. Our lab has made significant inroads in understanding the neuronal connectivity which subserves these sensory phenomena through experiments involving multiple markers to identify interactions between neural elements. Fos protenin coded by the c-fos proto-oncogene appears to be useful as a marker for neuronal activity. In a rat model of peripheral inflammation and hyperalgesia, Fos protein has been shown to increase in the nuclei of a subpopulation of neurons concentrated in laminae I, II and V, areas of the dorsal horn known to receive noxious inputs. Dynorphin, an opioid peptide which also up-regulates in the same animal model can be colocalized to a subpopulation of Fos-labeled neurons using either a double immunocytochemical method or immunocytochemistry in combination with in situ hybridization histochemistry. These data provide insights into the transcriptional events that occur in response to peripheral inflammation and hyperalgesia. A rat model of reduced small diameter primary afferent input to the spinal cord has been used to examine the role of these afferents in neuronal activation and behavioral responsivity in a rat model of peripheral inflammation and hyperalgesia. Capsaicin, injected neonatally into rat pups destroys a subpopulation of nociceptive primary afferent neurons. However, they retain their ability to behaviorally withdraw from noxious stimuli but exhibit less dorsal horn Fos activation than control animals. Thus inflammation-induced hyperalgesia likely involves non-capsaicin sensitive primary afferent axons while Fos activation appears to be closely related to capsaicin sensitive primary afferent axons.